The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies.

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles.

OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ±â€…12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.

Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck.

Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest and activity, only a few agents have been studied in Phase III trials (n = 6). The objective of this study was to identify common features that differentiate successful and failed Phase III OM trials. We used the United States Patent and Trademark Office Patent Public Search database to search patents with "oral mucositis" in the claims. We then searched ClinicalTrials.gov and PubMed to determine if Phase III or Phase II trial data for identified biologics/drugs had been published. We assessed each Phase III and Phase II trial for characteristics that may be associated with trial success or failure. We considered a study as a "success" if the primary endpoint reached statistical significance, and we considered a study as "failure" if the primary endpoint did not reach statistical significance. Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest.

Application of big data analyses to compare the impact of oral and gastrointestinal mucositis on risks and outcomes of febrile neutropenia and septicemia among patients hospitalized for the treatment of leukemia or multiple myeloma.

PURPOSE: Oral ulcerative mucositis (UM) and gastrointestinal mucositis (GIM) have been associated with increased likelihood of systemic infection (bacteremia and sepsis) in patients being treated for hematological malignancies. To better define and contrast differences between UM and GIM, we utilized the United States 2017 National Inpatient Sample and analyzed patients hospitalized for the treatment of multiple myeloma (MM) or leukemia. METHODS: We utilized generalized linear models to assess the association between adverse events-UM and GIM-among hospitalized MM or leukemia patients and the outcome of febrile neutropenia (FN), septicemia, burden of illness, and mortality. RESULTS: Of 71,780 hospitalized leukemia patients, 1255 had UM and 100 GIM. Of 113,915 MM patients, 1065 manifested UM and 230 had GIM. In an adjusted analysis, UM was significantly associated with increased risk of FN in both the leukemia (aOR = 2.87, 95% CI = 2.09-3.92) and MM cohorts (aOR = 4.96, 95% CI = 3.22-7.66). Contrastingly, UM had no effect on the risk of septicemia in either group. Likewise, GIM significantly increased the odds of FN in both leukemia (aOR = 2.81, 95% CI = 1.35-5.88) and MM (aOR = 3.75, 95% CI = 1.51-9.31) patients. Similar findings were noted when we restricted our analysis to recipients of high-dose condition regimens in preparation for hematopoietic stem-cell transplant. UM and GIM were consistently associated with higher burden of illness in all the cohorts. CONCLUSION: This first use of big data provided an effective platform to assess the risks, outcomes, and cost of care of cancer treatment-related toxicities in patients hospitalized for the management of hematologic malignancies.

Evolution of predictive risk factor analysis for chemotherapy-related toxicity.

The causes of variation in toxicity to the same treatment regimen among seemingly similar patients remain largely unknown. There was tremendous optimism that the patient's germline genome would be strongly predictive of treatment-related toxicity and could be used to personalize treatment and improve therapeutic outcomes. However, there has been limited success in discovering robust pharmacogenetic predictors of treatment-related toxicity and even less progress in translating the few validated predictors into clinical practice. It is apparent that identification of toxicity predictors that can be used to predict and prevent treatment-related toxicity will require thinking beyond germline genomics. To that end, we propose an integrated biomarker discovery approach that recognizes that a patient's toxicity risk is determined by the cumulative effects of a broad range of "omic" and non-omic factors. This commentary describes the limited success in discovering and translating clinical and pharmacogenetic toxicity predictors into clinical practice. We illustrate the evolution of cancer toxicity biomarker discovery and translation through studies of taxane-induced peripheral neuropathy, which is one of the most common and debilitating side effects of cancer treatment. We then discuss the opportunities for discovering non-genomic (e.g., metabolomic, lipidomic, transcriptomic, proteomic, microbiomic, medical, behavioral, environmental) and integrated biomarkers that may be more strongly predictive of toxicity risk and the potential challenges with translating integrated biomarkers into clinical practice. This integrated biomarker discovery approach may circumvent some of the major limitations in toxicity biomarker science and move precision oncology treatment forward so that patients receive maximum treatment benefit with minimal toxicity.

Identification of a SNP cluster associated with taxane-induced peripheral neuropathy risk in patients being treated for breast cancer using GWAS data derived from a large cooperative group trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytics to describe taxane-associated CIPN risk. METHODS: We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher's ratio (FR). We then ranked ordered those SNPs which discriminated CIPN-positive (CIPN +) from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross-validation (LOOCV). RESULTS: Using aggregated genotype data obtained from the previously reported ECOG-5103 clinical trial (in which two different arrays were used, HumanOmniExpress (727,227 SNPs) and HumanOmni1-Quad1 (1,131,857 SNPs)), we identified a 267 SNP cluster which was associated with a CIPN + phenotype with an accuracy of 96.1%. CONCLUSIONS: A cluster of SNPs was identified which prospectively discriminated patients most likely to develop symptomatic CIPN following taxane exposure as part of a breast cancer chemotherapy regimen. Validation using an independent patient cohort should be performed.

Leveraging GWAS data derived from a large cooperative group trial to assess the risk of taxane-induced peripheral neuropathy (TIPN) in patients being treated for breast cancer: Part 2-functional implications of a SNP cluster associated with TIPN risk in patients being treated for breast cancer.

INTRODUCTION: Using GWAS data derived from a large collaborative trial (ECOG-5103), we identified a cluster of 267 SNPs which predicted CIPN in treatment-naive patients as reported in Part 1 of this study. To assess the functional and pathological implications of this set, we identified collective gene signatures were and evaluated the informational value of those signatures in defining CIPN's pathogenesis. METHODS: In Part 1, we analyzed GWAS data derived from ECOG-5103, first identifying those SNPs that were most strongly associated with CIPN using Fisher's ratio. After identifying those SNPs which differentiated CIPN-positive from CIPN-negative phenotypes, we ranked them in order of their discriminatory power to produce a cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross validation (LOOCV). An uncertainty analysis was included. Using the best predictive SNP cluster, we performed gene attribution for each SNP using NCBI Phenotype Genotype Integrator and then assessed functionality by applying GeneAnalytics, Gene Set Enrichment Analysis, and PCViz. RESULTS: Using aggregate data derived from the GWAS, we identified a 267 SNP cluster which was associated with a CIPN+ phenotype with an accuracy of 96.1%. We could attribute 173 genes to the 267 SNP cluster. Six long intergenic non-protein coding genes were excluded. Ultimately, the functional analysis was based on 138 genes. Of the 17 pathways identified by Gene Analytics (GA) software, the irinotecan pharmacokinetic pathway had the highest score. Highly matching gene ontology attributions included flavone metabolic process, flavonoid glucuronidation, xenobiotic glucuronidation, nervous system development, UDP glycosyltransferase activity, retinoic acid binding, protein kinase C binding, and glucoronosyl transferase activity. Gene Set Enrichment Analysis (GSEA) GO terms identified neuron-associated genes as most significant (p = 5.45e-10). Consistent with the GA's output, flavone, and flavonoid associated terms, glucuronidation were noted as were GO terms associated with neurogenesis. CONCLUSION: The application of functional analyses to phenotype-associated SNP clusters provides an independent validation step in assessing the clinical meaningfulness of GWAS-derived data. Functional analyses following gene attribution of a CIPN-predictive SNP cluster identified pathways, gene ontology terms, and a network which were consistent with a neuropathic phenotype.

Differential associations of rheumatoid arthritis and periodontitis or tooth loss: A cross-sectional study.

AIM: To study the association between periodontitis, tooth loss, and rheumatoid arthritis (RA) by using a large national dataset. MATERIALS AND METHODS: An observational cross-sectional study was performed using the National Health and Nutrition Examination Survey cycles (2009-2014). RA status was detected using a questionnaire. Periodontal status was assigned on the basis of the clinical attachment level and periodontal pocket depth. Dentition status was assessed by the number of permanent teeth observed. We examined the association between RA as exposure and moderate/severe periodontitis and non-functional dentition as outcomes. We progressively adjusted our models for different sets of potential confounders. RESULTS: Moderate/severe periodontitis was more prevalent in participants reporting RA (53% vs. 41.5%, p = .0003). Non-functional dentition was more prevalent in participants with RA (41% vs. 15.5%, p = .0001). The fully adjusted model showed that participants with RA had higher odds of having non-functional dentition (odds ratio 1.8, 95% confidence interval [CI] 1.3-2.3, p = .0001) but no association with moderate/severe periodontitis (prevalence ratio 1.01, 95% CI 0.9-1.1, p = .9). CONCLUSION: RA was associated with a higher likelihood of having non-functional dentition but did not show any association with periodontitis after adjusting for the risk factors to control their confounding effect.

Psoriasis and oral health in adult United States population: a cross-sectional study.

OBJECTIVES: To detect the association between psoriasis as an exposure and oral health conditions as outcomes represented by periodontal and dentition status. This was addressed by analysis of a large number of adults in the United States. METHODS: By using The National Health and Nutrition Examination Survey datasets from 2009 to 2014, we performed a cross-sectional analysis of 11,726 participants included in our study population. For participants aged ≥ 30 years, the psoriasis status was assessed from the medical questionnaire. We used data from periodontal and oral examinations to assess the oral conditions of our participants. We examined the association between psoriasis as exposure and moderate/severe periodontitis and non-functional dentition as outcomes. RESULTS: The weighted prevalence of psoriasis was 3%, 44% for moderate/severe periodontitis, and 20.5% for non-functional dentition. The fully adjusted model showed no significant association between psoriasis and moderate/severe periodontitis (Prevalence Ratio 1.02, 95% CI 0.9-1.2, p = 0.8). There was no statistically significant association between psoriasis and non-functional dentition except in the fully adjusted model it became statistically significant (Prevalence Ratio 0.8, 95% CI 0.7-0.9, p = 0.04). CONCLUSION: Our results showed no association between psoriasis and periodontal or dentition status except in a fully adjusted model for non-functional dentition.

Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.

Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment over the past decade, improving survival rates in numerous advanced cancers. Immune-related adverse events (irAEs) are common and can affect any organ system, with many of these toxicities being well-characterized with clear grading criteria and management approaches. There has been less emphasis on oral manifestations of irAEs. This review provides an overview of oral manifestations of irAEs, including mucosal and salivary gland toxicities, and proposes a grading system and management guidelines. irAEs are common treatment-related toxicities in patients treated with ICIs. Oral irAEs can range from asymptomatic white reticulations to life-threatening mucocutaneous reactions requiring aggressive management with corticosteroids and/or permanent discontinuation of ICIs. Oral healthcare providers should be prepared to identify and manage oral irAEs in collaboration with oncologists and other specialists.

Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Oral side effects of immune checkpoint inhibitor therapy (ICIT): An analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana-Farber Cancer Institute, 2011 to 2019.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune-related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood. METHODS: Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed. Reports of oral conditions were categorized into oral mucosal disorders, xerostomia, and dysgeusia. After applying exclusion criteria, demographic characteristics and clinical features were summarized for the patients who had oral irAEs. RESULTS: In total, 317 patients developed oral conditions that were associated with ICIT (incidence, 6.8%; 317 of 4683 patients). These conditions included xerostomia (68.5%), oral mucosal disorders (33.4%), and dysgeusia (24.0%). In patients with oral irAEs, respiratory cancer (28.4%) was the most common primary cancer, followed by melanoma (26.2%), and head and neck cancer (14.8%). Oral mucosal disorders developed after the initiation of ICIT between 2 and 851 days (between 1 and 1332 days in patients with xerostomia and between 1 and 1455 days in patients with dysgeusia). Of all oral irAEs, 50.9% developed within 3 months, and 85.5% developed within 12 months. CONCLUSIONS: Oral side effects appear to be more common among patients who receive ICIT than has been previously reported. Concomitant cytotoxic regimens may exacerbate the risk of oral adverse events, perhaps representing the sum of the effects of different, but simultaneous or sequential, pathogenic mechanisms. Additional studies are warranted to better characterize oral irAEs and their biologic basis.

Treatment for Oral Mucositis-Current Options and an Update of Small Molecules Under Development.

OPINION STATEMENT: Despite its history as one of the most impactful toxicities associated with cytotoxic cancer therapy, oral mucositis (OM) remains an unmet clinical need which affects hundreds of thousands of patients. Descriptions of its complex pathogenesis have provided mechanistic targets which are being exploited to develop an effective therapeutic intervention. Favorable results of recently completed clinical trials in which agents focused on interrupting the early stages of the mucositis biological cascade were assessed provide reason for optimism, not only for oral mucositis but also for halo indications which share its pathobiogenesis.

A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment.

Oral mucositis (OM) remains a significant unmet need for patients being treated with standard concomitant chemoradiation (CRT) regimens for head and neck cancers (HNC). OM's pathogenesis is complex and includes both direct and indirect damage pathways. In this paper, the field is reviewed with emphasis on the initiating and sustaining role of oxidative stress on OM's pathobiology. A hypothesis is presented which suggests that based on OM's clinical and biological trajectory, mucosal damage is largely the consequence of cumulative CRT-induced biological changes overwhelming physiologic self-protective mechanisms. Furthermore, an individual's ability to mount and maintain a protective response is dependent on interacting pathways which are primarily determined by a multiplex consisting of genomics, epigenomics, and microbiomics. Effective biologic or pharmacologic OM interventions are likely to supplement or stimulate existing physiologic damage-control mechanisms.

Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers.

BACKGROUND: The ability to consistently and accurately assess oral mucositis (OM) is critical to descriptions of its incidence and severity and in evaluating the effectiveness of potential interventions. The lack of a single grading scale compounds outcome interpretation. Consequently, we assessed the concordance of three of the most commonly used OM grading criteria (World Health Organization (WHO), Radiation Therapy Oncology Group (RTOG), and the common terminology criteria for adverse events (CTCAE). METHODS: Data was evaluated from two hundred patients with oropharyngeal or oral cavity cancers who underwent chemoradiation therapy and were enrolled in a double-blind, randomized, placebo-controlled trial in which trained assessors evaluated patients twice weekly. WHO, RTOG, and CTCAE scores were assigned centrally by independent evaluators blinded to the study group. Concordance among the three scales for all OM scores and severe OM scores (score ≥ 3) was defined as the percentage agreement and measured using Cohen's weighted Kappa. RESULTS: Of 3,578 OM assessments, 57% had identical scores for all three scales. When any score was considered, the concordance between WHO and RTOG scales was 71% (kappa 0.58; 95%CI: 0.56-0.60), 62% for the WHO and CTCAE scales (kappa 0.46; 95%CI: 0.44-0.48) and 78% for the CTCAE and RTOG scales (kappa 0.69; 95%CI: 0.68-0.71). When patients had severe OM (WHO score ≥ 3), 99.6% (521/523) of the CTCAE OM assessments had scores of 3 or 4 (kappa 0.98; 95%CI: 0.98-0.999) and 97.7% of the RTOG ones (511/523) had scores of 3 or 4 (kappa 0.69; 95%CI: 0.62-0.75). Among patients who had a WHO score of 4, 31.7% (63/199) and 96.0% (196/199) of patients had RTOG or CTCAE scores of 2 or 3, respectively. CONCLUSIONS: Discordance was seen with patients who exhibited mild to moderate OM or most severe OM (grade 4) as described by WHO criteria. Whereas scale selection seems less critical in studies in which general "severe mucositis" is the primary outcome, it is particularly important in accurately describing OM's clinical trajectory and the frequency and impact in its most severe forms.

Network meta-analysis from a pairwise meta-analysis design: to assess the comparative effectiveness of oral care interventions in preventing ventilator-associated pneumonia in critically ill patients.

OBJECTIVE: In this research, we assessed the usefulness of network meta-analysis (NMA), in creating a hierarchy to define the most effective oral care intervention for the prevention and management of ventilation-associated pneumonia (VAP). MATERIALS AND METHODS: We applied NMA to a previously published robust pairwise meta-analysis. Statistical analyses were based on comparing rates of total VAP events between intervention groups and placebo-usual care groups. We synthesized a netgraph, reported the ranking order of the interventions, and summarized output by a forest plot with a reference treatment placebo/usual care. RESULTS: The results of this NMA are from the low and high risk of bias studies, and hence, we strongly recommend not to use findings of this NMA for clinical treatment needs, but based on results of the NMA, we highly recommend for future clinical trials. With our inclusion and exclusion criteria for the NMA, we extracted 25 studies (4473 subjects). The NMA included 16 treatments, 29 pairwise comparisons, and 15 designs. Based on results of NMA frequentist-ranking P scores, tooth brushing (P fixed-0.94, P random-0.89), tooth brushing with povidone-iodine (P fixed-0.90, P random-0.88), and furacillin (P fixed-0.88, P random-0.84) were the best three interventions for preventing VAP. CONCLUSIONS: Any conclusion drawn from this NMA should be taken with caution and recommend future clinical trials with the results. CLINICAL RELEVANCE: NMA appeared to be an effective platform from which multiple interventions reported in disparate clinical trials could be compared to derive a hierarchical assessment of efficacy in VAP intervention.

Robust pathway sampling in phenotype prediction. Application to triple negative breast cancer.

BACKGROUND: Phenotype prediction problems are usually considered ill-posed, as the amount of samples is very limited with respect to the scrutinized genetic probes. This fact complicates the sampling of the defective genetic pathways due to the high number of possible discriminatory genetic networks involved. In this research, we outline three novel sampling algorithms utilized to identify, classify and characterize the defective pathways in phenotype prediction problems, such as the Fisher's ratio sampler, the Holdout sampler and the Random sampler, and apply each one to the analysis of genetic pathways involved in tumor behavior and outcomes of triple negative breast cancers (TNBC). Altered biological pathways are identified using the most frequently sampled genes and are compared to those obtained via Bayesian Networks (BNs). RESULTS: Random, Fisher's ratio and Holdout samplers were more accurate and robust than BNs, while providing comparable insights about disease genomics. CONCLUSIONS: The three samplers tested are good alternatives to Bayesian Networks since they are less computationally demanding algorithms. Importantly, this analysis confirms the concept of "biological invariance" since the altered pathways should be independent of the sampling methodology and the classifier used for their inference. Nevertheless, still some modifications are needed in the Bayesian networks to be able to sample correctly the uncertainty space in phenotype prediction problems, since the probabilistic parameterization of the uncertainty space is not unique and the use of the optimum network might falsify the pathways analysis.

Correction to: Could the impact of photobiomodulation on tumor response to radiation be effected by tumor heterogeneity?

The Editor wishes to clarify that the author of the above named Commentary provided an ICMJE Conflict of Interest form at the time of submission.

Impact of the insurance type of head and neck cancer patients on their hospitalization utilization patterns.

BACKGROUND: Head and neck cancer (HNC) patients with Medicaid, Medicare, or no insurance show poor outcomes in comparison with privately insured patients. It was hypothesized that nonprivate insurance coverage biases the selection of the treatment site to favor hospitals that are not associated with optimum treatment outcomes. This study assessed the relation between the insurance type of HNC patients and the hospital type for inpatient care. METHODS: Adult HNC patients were identified from the Nationwide Inpatient Sample (2012 and 2013). The primary exposure was the insurance provider type. The outcome was the hospital type, which was classified by the hospital's ownership and its location and teaching status. Multivariate multinomial logistic regression models were constructed to control for the patient's age, sex, race, income, mortality risk, and geographic location. The analysis was weighted and was adjusted for multiple comparisons. RESULTS: In all, 37,466 HNC patients representing 187,330 patients nationally were identified. After adjustments for age, sex, race, income, and mortality risk, in comparison with privately insured patients, Medicaid, Medicare, and uninsured patients demonstrated 1.14 to 2.29 increased odds of undergoing treatment at rural, urban nonteaching, private investor-owned, or government (nonfederal) hospitals (P < .05). This trend remained apparent even after adjustments for the geographic location. CONCLUSIONS: Uninsured patients or patients insured by government programs predominantly underwent care for HNC at hospital types most often associated with inferior survival outcomes. This finding could explain some proportion of insurance-related disparities in HNC outcomes. Further studies are warranted to determine whether interventions to promote equitable access to optimal hospital settings for patients, regardless of their insurance type, might improve outcomes among nonprivate insurance holders. Cancer 2018;124:760-8. © 2017 American Cancer Society.

The Use of Hyperbaric Oxygen for the Prevention and Management of Osteoradionecrosis of the Jaw: A Dana-Farber/Brigham and Women's Cancer Center Multidisciplinary Guideline.

BACKGROUND: Osteoradionecrosis of the jaw (ORN) is an infrequent yet potentially devastating complication of radiation therapy to the head and neck region. Treatment options include antimicrobial therapy, local sequestrectomy, resection, and the use of hyperbaric oxygen (HBO). Published data on ORN are difficult to compare because of the lack of a universally accepted classification and staging system, and the literature on the use of HBO to either prevent or successfully manage ORN is controversial and inconclusive. Therefore, we aimed to establish a standard approach for using HBO at our institution. MATERIALS AND METHODS: A literature search was conducted of articles published in the English language between January 1980 and January 2016. Retrieved articles were evaluated by two independent reviewers. Isolated case reports, abstracts, case series, review articles, and cohort studies without a control group were excluded; summary data were extracted from the remaining studies. A panel of experts from Head and Neck Oncology and Oral Medicine from the Dana-Farber Cancer Institute and Brigham and Women's Hospital reviewed the summary data and established multidisciplinary guidelines on the use of HBO for the prevention and management of ORN. RESULTS: Seven studies were evaluated and reviewed by the multidisciplinary panel. There was no consistent evidence in support of HBO for either the prevention or management of ORN. CONCLUSION: Based on the available evidence and expert opinion, routine use of HBO for the prevention or management of ORN is not recommended and is rarely used at our institution. The Oncologist 2017;22:343-350 IMPLICATIONS FOR PRACTICE: The Division of Head and Neck Oncology of Dana-Farber/Brigham and Women's Cancer Center does not recommend the routine use of HBO for the prevention or management of ORN. Adjunctive HBO may be considered for use on a case-by-case basis in patients considered to be at exceptionally high risk who have failed conservative therapy and subsequent surgical resection.